Abstract
The first two steps in the capping of cellular mRNAs are catalyzed by the enzymes RNA triphosphatase and RNA guanylyltransferase. Although structural and mechanistic differences between fungal and mammalian RNA triphosphatases recommend this enzyme as a potential antifungal target, it has not been determined if RNA triphosphatase is essential for the growth of fungal species that cause human disease. We show by classical genetic methods that the triphosphatase (Pct1) and guanylyltransferase (Pce1) components of the capping apparatus in the fission yeast Schizosaccharomyces pombe are essential for growth. We were unable to disrupt both alleles of the Candida albicans RNA triphosphatase gene CaCET1, implying that the RNA triphosphatase enzyme is also essential for growth of C. albicans, a human fungal pathogen. Our results provide the first genetic evidence that cap synthesis is essential for growth of an organism other than Saccharomyces cerevisiae and they validate RNA triphosphatase as a target for antifungal drug discovery.
Highlights
The first two steps in the capping of cellular mRNAs are catalyzed by the enzymes RNA triphosphatase and RNA guanylyltransferase
We conclude that the RNA triphosphatase and RNA guanylyltransferase genes are essential for cell growth in S. pombe
We have shown that the RNA triphosphatases Pct1 and CaCet1 are essential for viability of S. pombe and C. albicans, respectively The conclusion that CaCet1 is essential is based on a finding that none of the 54 independent isolates in the single-transformation test were homozygous for cacet1∆; our interpretation is consistent with criteria established by Mitchell and colleagues for inference of essentiality using this genetic approach
Summary
The first two steps in the capping of cellular mRNAs are catalyzed by the enzymes RNA triphosphatase and RNA guanylyltransferase. Structural and mechanistic differences between fungal and mammalian RNA triphosphatases recommend this enzyme as a potential antifungal target, it has not been determined if RNA triphosphatase is essential for the growth of fungal species that cause human disease. The three capping reactions are universal in eukaryotes, there is a surprising diversity in the genetic organization of the capping enzymes as well as a complete divergence in the structure and catalytic mechanism of the RNA triphosphatase component in "lower" versus "higher" eukaryotic species [1]. The primary structures and biochemical mechanisms of the fungal and mammalian guanylyltransferases and cap methyl-. The atomic structures and catalytic mechanisms of the fungal and mammalian RNA triphosphatases are completely different [2,3]. It has been suggested that RNA triphosphatase is a promising target for antifungal drug discovery [2]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
